970 Million Druglike Small Molecules for Virtual Screening in the Chemical Universe Database GDB-13

Blum, Lorenz C.; Reymond, Jean‐Louis

doi:10.1021/ja902302h

Cited by 681 publications

(642 citation statements)

References 32 publications

(17 reference statements)

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“…[8][9][10][11] The exponential scaling of their number is also evident for the recently published exhaustive list of small organic molecules. [12] This is the regime in which isomerism occurs through conventional ' 'chemistry,' ' that is, chemical reactions that lead from one constitutional isomer to another, usually under the influence of pressure, temperature, light, or some catalytic agent. We can model this and the subsequent regimes iii and iv using ab initio molecular dynamics methods.…”

Section: Energy Hierarchymentioning

confidence: 99%

First principles view on chemical compound space: Gaining rigorous atomistic control of molecular properties

Lilienfeld

2013

Int J of Quantum Chemistry

138

160

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A well‐defined notion of chemical compound space (CCS) is essential for gaining rigorous control of properties through variation of elemental composition and atomic configurations. Here, we give an introduction to an atomistic first principles perspective on CCS. First, CCS is discussed in terms of variational nuclear charges in the context of conceptual density functional and molecular grand‐canonical ensemble theory. Thereafter, we revisit the notion of compound pairs, related to each other via “alchemical” interpolations involving fractional nuclear charges in the electronic Hamiltonian. We address Taylor expansions in CCS, property nonlinearity, improved predictions using reference compound pairs, and the ounce‐of‐gold prize challenge to linearize CCS. Finally, we turn to machine learning of analytical structure property relationships in CCS. These relationships correspond to inferred, rather than derived through variational principle, solutions of the electronic Schrödinger equation. © 2013 Wiley Periodicals, Inc.

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Section: Energy Hierarchymentioning

confidence: 99%

First principles view on chemical compound space: Gaining rigorous atomistic control of molecular properties

Lilienfeld

2013

Int J of Quantum Chemistry

138

160

View full text Add to dashboard Cite

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“…In this manner, the link between the strutural formula of a compound and its position in MQN-space is self-explanatory. Furthermore, MQN-calculations are extremely fast and therefore particularly well suited to classify very large databases such as PubChem, which contains over 20 million structures, or the chemical universe database GDB-13 which contains 977 million structures as shown in the following paper in this issue [22][23][24][25]. The MQN-system is also relevant for medicinal chemistry, as illustrated by the fact that similarity searches in MQN-space enrich bioactives in the DUD database [26] from the entire PubChem with efficiencies comparable to that of substructure fingerprints, with the added benefit that lead-hopping relationships between actives are allowed [27].…”

Section: Introductionmentioning

confidence: 99%

Visualisation of the chemical space of fragments, lead-like and drug-like molecules in PubChem

Deursen

Blum

Reymond

2011

J Comput Aided Mol Des

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The 4.5 million organic molecules with up to 20 non-hydrogen atoms in PubChem were analyzed using the MQN-system, which consists in 42 integer value descriptors of molecular structure. The 42-dimensional MQN-space was visualised by principal component analysis and representation of the (PC1, PC2), (PC1, PC3) and (PC2, PC3) planes. The molecules were organized according to ring count (PC1, 38% of variance), the molecular size (PC2, 25% of variance), and the H-bond acceptor count (PC3, 12% of variance). Compounds following Lipinski's bioavailability, Oprea's lead-likeness and Congreve's fragment-likeness criteria formed separated groups in MQN-space visible in the (PC2, PC3) plane. MQN-similarity searches of the 4.5 million molecules (see the browser available at www.gdb.unibe.ch) gave significant enrichment factors for recovering groups of fragment-sized bioactive compounds related to ten different biological targets taken from Chembl, allowing leadhopping relationships not seen with substructure fingerprint similarity searches. The diversity of different compound series was analyzed by MQN-distance histograms.

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“…45 Finally, the combination of heuristic rules and quantum chemical calculations might be viewed as an expedient tool for exploring chemically accessible regions of chemical space. 31,[72][73][74] Coupled with efficient quantum chemical methodology and high-throughput computation, it holds promise for novel approaches for molecular design and optimization.…”

Section: Probing the Chemistry Of The Formose Reaction Networkmentioning

confidence: 99%

Complex Chemical Reaction Networks from Heuristics-Aided Quantum Chemistry

Rappoport

Galvin

Zubarev

et al. 2014

J. Chem. Theory Comput.

127

155

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While structures and reactivities of many small molecules can be computed efficiently and accurately using quantum chemical methods, heuristic approaches remain essential for modeling complex structures and large-scale chemical systems. Here we present heuristics-aided quantum chemical methodology applicable to complex chemical reaction networks such as those arising in metabolism and prebiotic chemistry. Chemical heuristics offer an expedient way of traversing high-dimensional reactive potential energy surfaces and are combined here with quantum chemical structure optimizations, which yield the structures and energies of the reaction intermediates and products. Application of heuristics-aided quantum chemical methodology to the formose reaction of prebiotic evolution reproduces the experimentally observed reaction products, major reaction pathways, and autocatalytic cycles.

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970 Million Druglike Small Molecules for Virtual Screening in the Chemical Universe Database GDB-13

Abstract: GDB-13 enumerates small organic molecules containing up to 13 atoms of C, N, O, S, and Cl following simple chemical stability and synthetic feasibility rules. With 977,468,314 structures, GDB-13 is the largest publicly available small organic molecule database to date.

Cited by 681 publications

References 32 publications

First principles view on chemical compound space: Gaining rigorous atomistic control of molecular properties

First principles view on chemical compound space: Gaining rigorous atomistic control of molecular properties

Visualisation of the chemical space of fragments, lead-like and drug-like molecules in PubChem

Complex Chemical Reaction Networks from Heuristics-Aided Quantum Chemistry

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